Modified lipidated Relaxin B chain peptides and their therapeutic use

Abstract

or a salt or solvate thereof. Also provided is a pharmaceutical composition comprising at least one peptide of the invention, and the peptide or the pharmaceutical composition for its use as a medicament.

The invention claimed is: 
     
       1. A peptide having the following formula (I):
   N ter -Ac-(E) a -X 10 -E-G-R-E-X 15 -V-R-X 18 -X 19 -I-X 21 -X 22 -E-G-X 25 -S-X 27 -X 28 -X 29 -X 30 -R-(X 32 ) b -(X 33 ) c -(K) d -(X 35 ) e -(gE) f -X 37 -C ter ; 
 wherein: 
 N ter  represents the N-terminal end of the peptide; 
 C ter  represents the C-terminal end of the peptide; 
 a, b, c and d independently represent 0 or 1; 
 e and f independently represents 0, 1, 2, 3 or 4; 
 Ac represents acetyl group; 
 E represents glutamic acid; 
 X 10  represents an amino acid selected from the group consisting of leucine, 
 2-amino-isobutyric acid, Nε-acetyl-lysine and α-methyl-leucine; 
 G represents glycine; 
 R represents arginine; 
 X 15  represents an amino acid selected from the group consisting of lysine, homolysine, arginine, homoarginine and ornithine; 
 V represents valine; 
 X 18  represents an amino acid selected from the group consisting of alanine, 2-amino-isobutyric acid, leucine, Nε-acetyl-lysine, and glutamine; 
 X 19  represents an amino acid selected from the group consisting of glutamine, Nε-acetyl-lysine, citruline, alanine and 2-amino-isobutyric acid; 
 I represents isoleucine; 
 X 21  represents an amino acid selected from the group consisting of alanine and 2-amino-isobutyric acid; 
 X 22  represents an amino acid selected from the group consisting of isoleucine and 2-amino-isobutyric acid; 
 X 25  represents an amino acid selected from the group consisting of methionine, norleucine, leucine, alanine, glutamine, Nε-acetyl-lysine and glutamic acid; 
 S represents serine; 
 X 27  represents an amino acid selected from the group consisting of threonine, lysine, arginine and glutamine; 
 X 28  represents an amino acid selected from the group consisting of tryptophan, 5-fluoro-tryptophan, 5-chloro-tryptophan, 5-methoxy-tryptophan, tyrosine, phenylalanine, 4-fluoro-phenylalanine, 1-naphtylalanine, 2-naphtylalanine, α-methyl-tryptophane, α-methyl-phenylalanine and 5-hydroxy-tryptophane; 
 X 29  represents an amino acid selected from the group consisting of serine, threonine, α-methyl-serine, Nε-acetyl-lysine and valine; 
 X 30  represents an amino acid selected from the group consisting of lysine, 2-amino-isobutyric acid, α-methyl-lysine, arginine and α-methyl-arginine; 
 X 31  represents an amino acid selected from the group consisting of arginine, Nω-methyl-arginine, alanine, Nω,Nω′-dimethyl-arginine and citruline; 
 X 32  represents an amino acid selected from the group consisting of lysine, Nε-acetyl-lysine, arginine, alanine and Nε,Nε,Nε-tri-methyl-lysine; 
 X 33  represents an amino acid selected from the group consisting of leucine, lysine, Nε-acetyl-lysine, alanine and arginine; 
 K represents lysine; 
 X 35  represents a polyethylene glycol derivative selected from the group consisting of PEG 2 , PEG 4 , PEG 8 , PEG 2 DGA, TTDS, PEG 12 , PEG 24  and PEG 8 ; 
 gE represents gamma-glutamic acid; 
 and 
 X 37  represents the following structure: 
 
       
         
           
           
               
               
           
         
         in which:
 -* represents a covalent bond: with (gE) f  when f is different from 0; with (X 35 ) e  when f is 0 and e is different from 0; with (K) d  when e and f are 0 and d is 1; with (X 33 ) c  when d, e and f are 0 and c is 1; with (X 32 ) b  when c, d, e and f are 0 and b is 1; or with X 31  when b, c, d, e and f all are 0; and 
 
         Z represents a group of formula (II):
   -[(PEG xx ) g ( g E) h (PEG xx ) i ( g E) J C k ] 
 in which: 
 g and i independently represent 0, 1, 2, 3, 4 or 5; 
 h and j independently represent 0, 1, 2, 3, 4 or 5; 
 PEGxx independently represents a polyethylene glycol derivative selected from the group 
 consisting of PEG 2 , PEG 2 DGA, TTDS and PEG 12 ; and 
 C k  represents a linear saturated C 12 —C 22  acyl group; 
 
         or a salt or solvate thereof. 
       
     
     
       2. The peptide according to  claim 1  having the following formula (Ia):
   N ter -Ac-(E) a -L-E-G-R-E-K-V-R-X 18 -X 19 -I-Aib-Aib-E-G-X 25 -S-T-X 28 -X 29 -X 30 -X 31 -(X 32 ) b -(X 33 ) c -(K) d -(X 35 ) e -(gE) f -X 37 -C ter    
 wherein: 
 N ter  represents the N-terminal end of the peptide; 
 C ter  represents the C-terminal end of the peptide; 
 a, b, c and d independently represent 0 or 1; 
 e represents 0, 1, 2, 3 or 4; 
 f represents 0, 2 or 3; 
 Ac represents acetyl group; 
 E represents glutamic acid; 
 L represents leucine; 
 G represents glycine; 
 R represents arginine; 
 K represents lysine; 
 V represents valine; 
 X 18  represents an amino acid selected from the group consisting of alanine, 2-amino-isobutyric acid and leucine; 
 X 19  represents an amino acid selected from the group consisting of glutamine, Nε-acetyl-lysine and alanine; 
 I represents isoleucine; 
 Aib represents 2-amino-isobutyric acid; 
 X 25  represents an amino acid selected from the group consisting of methionine, norleucine, glutamine, Nε-acetyl-lysine and glutamic acid; 
 S represents serine; 
 T represents threonine; 
 X 28  represents an amino acid selected from the group consisting of tryptophan, 1-naphtylalanine, phenylalanine, tyrosine, α-methyl-tryptophane, α-methyl-phenylalanine and 5-hydroxy-tryptophane; 
 X 29  represents an amino acid selected from the group consisting of serine, threonine and α-methyl-serine; 
 X 30  represents an amino acid selected from the group consisting of lysine, 2-amino-isobutyric acid and α-methyl-lysine; 
 X 31  represents an amino acid selected from the group consisting of arginine, Nω-methyl-arginine, alanine, Nω,Nω′-dimethyl-arginine and citruline; 
 X 32  represents an amino acid selected from the group consisting of lysine, alanine, Nε-acetyl-lysine and Nε,Nε,Nε-tri-methyl-lysine; 
 X 33  represents an amino acid selected from the group consisting of leucine, lysine and Nε-acetyl-lysine; 
 X 35  represents a polyethylene glycol derivative selected from the group consisting of PEG 2 , PEG 4 , PEG 8 , PEG 2 DGA, TTDS, PEG 12 , PEG 24  and PEG 28 ; 
 gE represents gamma-glutamic acid; 
 and 
 X 37  represents the following structure: 
 
       
         
           
           
               
               
           
         
         
           in which: 
           -* is as defined in  claim 1 ; and 
           Z is selected from the group consisting of a -palmitoyl (-Palm), -gamma glutamic acid-palmitoyl (-gE-Palm), -gamma glutamic acid-stearoyl (-gE-Stea), -(gamma glutamic acid) 2 -palmitoyl (-(gE) 2 -Palm), -(gamma glutamic acid) 3 -palmitoyl (-(gE) 3 -Palm), -(gamma glutamic acid) 3 -stearoyl (-(gE) 3 -Stea), -(gamma glutamic acid) 4 -stearoyl (-(gE) 4 -Stea), -(gamma glutamic acid) 4 -plamitoyl (-(gE) 4 -Palm), -stearoyl (-stea), -PEG 2 -Palmitoyl (-PEG 2 -Palm), -(PEG 2 ) 2 -Stearoyl (-(PEG 2 ) 2 -Stea), -(PEG 2 ) 3 -Stearoyl (-(PEG 2 ) 3 -Stea), -PEG 2 -(gamma glutamic acid)-Palmitoyl (-PEG 2 -gE-Palm), -PEG 2 -(gamma glutamic acid) 2 -Palmitoyl (-PEG 2 -(gE) 2 -Palm), -PEG 2 -(gamma glutamic acid) 3 -Palmitoyl (-PEG 2 -(gE) 3 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -gE-Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -Palmitoyl (-(PEG 2 ) 2 -(gE) 2 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 2 -(gE) 3 -Palm), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 3 -(gE) 3 -Palm), -(PEG 2 ) 4 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 4 -(gE) 3 -Palm), -(PEG 2 ) 3 -(gamma glutamic acid) 4 -Palmitoyl (-(PEG 2 ) 3 -(gE) 4 -Palm), -PEG 12 -(gamma glutamic acid) 3 -Palmitoyl (-PEG 12 -(gE) 3 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 2 -(gE) 3 -Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 3 -(gE) 3 -Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 4 -Stearoyl (-(PEG 2 ) 3 -(gE) 4 -Stea), -(PEG 2 ) 4 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 4 -(gE) 3 -Stea), -(PEG 2 ) 5 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 5 -(gE) 3 -Stea), -(PEG 2 DGA)-(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA)-(gE) 3 -Stea), -(PEG 2 DGA) 2 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA) 2 -(gE) 3 -Stea), -(PEG 2 DGA) 3 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA) 3 -(gE) 3 -Stea), -PEG 12 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 12 )-(gE) 3 -Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -PEG 2 -Stearoyl (-(PEG 2 ) 2 -(gE) 3 -PEG 2 -Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -PEG 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -(gE) 2 -PEG 2 -(gE)-Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -PEG 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -(gE) 3 -PEG 2 -(gE)-Stea), -(gamma glutamic acid) 2 -(PEG 2 ) 2 -(gamma glutamic acid)-Stearoyl (-(gE) 2 -(PEG 2 ) 2 -(gE)-Stea), -(gamma glutamic acid) 2 -(PEG 2 ) 3 -(gamma glutamic acid)-Stearoyl (-(gE) 2 -(PEG 2 ) 3 -(gE)-Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 5 -Stearoyl (-(PEG 2 ) 3 -(gE) 5 -Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Lauroyl (-(PEG 2 ) 3 -(gE) 3 -Lau), -(gamma glutamic acid) 5 -stearoyl (-(gE) 5 -Stea), -(PEG 2 ) 4 -(gamma glutamic acid) 4 -Palmitoyl (-(PEG 2 ) 4 -(gE) 4 -Palm), -(gamma glutamic acid) 4 -Lauroyl (-(gE) 4 -Lau), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Pentadecanoyl (-(PEG 2 ) 3 -(gE) 3 -Penta), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Heptadecanoyl (-(PEG 2 ) 3 -(gE) 3 -Hepta), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -PEG 2 -(gamma glutamic acid)-Palmitoyl (-(PEG 2 ) 2 -(gE) 2 -PEG 2 -(gE)-Palm), -(TTDS) 2 -(gamma glutamic acid) 3 -Palmitoyl (-(TTDS) 2 -(gE) 3 -Palm), -(gamma glutamic acid) 4 -Pentadecanoyl (-(gE) 4 -Penta), -(gamma glutamic acid) 2 -Pentadecanoyl (-(gE) 2 -Penta), -(gamma glutamic acid) 4 -Myristoyl (-(gE) 4 -Myr), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Myristoyl (-(PEG 2 ) 3 -(gE) 3 -Myr), -(PEG 2 ) 4 -(gamma glutamic acid) 4 -Stearoyl (-(PEG 2 ) 4 -(gE) 4 -Stea), -(TTDS) 3 -(gamma glutamic acid) 3 -Palmitoyl (-(TTDS) 3 -(gE) 3 -Palm), -(gamma glutamic acid) 3 -Pentadecanoyl (-(gE) 3 -Penta), -(TTDS) 3 -(gamma glutamic acid) 3 -Pentadecanoyl (-(TTDS) 3 -(gE) 3 -Penta), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Eicosanoyl ((-PEG 2 ) 3 -(gE) 3 -Eico) and -(PEG 2 ) 3 -(gamma glutamic acid) 3 -docosanoyl ((-PEG 2 ) 3 -(gE) 3 -Doco), 
         
         or a salt or solvate thereof. 
       
     
     
       3. The peptide according to  claim 1 , wherein it has an amino acid sequence selected from the group consisting of the amino acid sequences of reference SEQ ID NO: 1-193. 
     
     
       4. The peptide according to  claim 1 , wherein (X 35 ) e  represents a polyethylene glycol derivative selected from the group consisting of PEG 2 , (PEG 2 ) 2 , (PEG 2 ) 3 , (PEG 2 ) 4 , PEG 2 DGA, (PEG 2 DGA) 2 , (PEG 2 DGA) 3 , (TTDS) 2 , (TTDS) 3 , PEG 4 , (PEG 4 ) 2 , PEG 8 , PEG 12 , PEG 24  and PEG 28  or a salt or solvate thereof. 
     
     
       5. The peptide according to  claim 1 , wherein Z is selected from the group consisting of -gamma glutamic acid-palmitoyl (-gE-Palm), -(gamma glutamic acid) 2 -palmitoyl (-(gE) 2 -Palm), -(gamma glutamic acid) 3 -palmitoyl (-(gE) 3 -Palm), -(gamma glutamic acid) 3 -stearoyl (-(gE) 3 -Stea), -(gamma glutamic acid) 4 -stearoyl (-(gE) 4 -Stea), -(gamma glutamic acid) 4 -plamitoyl (-(gE) 4 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -gE-Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -Palmitoyl (-(PEG 2 ) 2 -(gE) 2 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 2 -(gE) 3 -Palm), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 3 -(gE) 3 -Palm), -(PEG 2 ) 4 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 4 -(gE) 3 -Palm), -(PEG 2 ) 3 -(gamma glutamic acid) 4 -Palmitoyl (-(PEG 2 ) 3 -(gE) 4 -Palm), -PEG 12 -(gamma glutamic acid) 3 -Palmitoyl (-PEG 12 -(gE) 3 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 2 -(gE) 3 -Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 3 -(gE) 3 -Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 4 -Stearoyl (-(PEG 2 ) 3 -(gE) 4 -Stea), -(PEG 2 ) 4 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 4 -(gE) 3 -Stea), -(PEG 2 ) 5 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 5 -(gE) 3 -Stea), -(PEG 2 DGA)-(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA)-(gE) 3 -Stea), -(PEG 2 DGA) 2 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA) 2 -(gE) 3 -Stea), -(PEG 2 DGA) 3 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA) 3 -(gE) 3 -Stea), -PEG 12 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 12 )-(gE) 3 -Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -PEG 2 -Stearoyl (-(PEG 2 ) 2 -(gE) 3 -PEG 2 -Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -PEG 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -(gE) 2 -PEG 2 -(gE)-Stea), -(PEG) 2 -(gamma glutamic acid) 3 -PEG 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -(gE) 3 -PEG 2 -(gE)-Stea), -(gamma glutamic acid) 2 -(PEG 2 ) 2 -(gamma glutamic acid)-Stearoyl (-(gE) 2 -(PEG 2 ) 2 -(gE)-Stea), -(gamma glutamic acid) 2 -(PEG 2 ) 3 -(gamma glutamic acid)-Stearoyl (-(gE) 2 -(PEG 2 ) 3 -(gE)-Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 5 -Stearoyl (-(PEG 2 ) 3 -(gE) 5 -Stea), -(gamma glutamic acid) 5 -Stearoyl (-(gE) 5 -Stea), -(PEG 2 ) 4 -(gamma glutamic acid) 4 -Palmitoyl (-(PEG 2 ) 4 -(gE) 4 -Palm); -(gamma glutamic acid) 4 -Lauroyl (-(gE) 4 -Lau), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Pentadecanoyl (-(PEG 2 ) 3 -(gE) 3 -Penta), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Heptadecanoyl (-(PEG 2 ) 3 -(gE) 3 -Hepta), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -PEG 2 -(gamma glutamic acid)-Palmitoyl (-(PEG 2 ) 2 -(gE) 2 -PEG 2 -(gE)-Palm), -(TTDS) 2 -(gamma glutamic acid) 3 -Palmitoyl (-(TTDS) 2 -(gE) 3 -Palm), -(gamma glutamic acid) 4 -Pentadecanoyl (-(gE) 4 -Penta), -(gamma glutamic acid) 2 -Pentadecanoyl (-(gE) 2 -Penta), -(gamma glutamic acid) 4 -Myristoyl (-(gE) 4 -Myr), -(PEG 2 ) 4 -(gamma glutamic acid) 4 -Stearoyl (-(PEG 2 ) 4 -(gE) 4 -Stea), -(TTDS) 3 -(gamma glutamic acid) 3 -Palmitoyl (-(TTDS) 3 -(gE) 3 -Palm), -(gamma glutamic acid) 3 -Pentadecanoyl (-(gE) 3 -Penta), -(TTDS) 3 -(gamma glutamic acid) 3 -Pentadecanoyl (-(TTDS) 3 -(gE) 3 -Penta), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Eicosanoyl ((-PEG 2 ) 3 -(gE) 3 -Eico) and -(PEG 2 ) 3 -(gamma glutamic acid) 3 -docosanoyl ((-PEG 2 ) 3 -(gE) 3 -Doco); or a salt or solvate thereof. 
     
     
       6. The peptide according to  claim 1  of formula (Ia), wherein:
 N ter  represents the N-terminal end of the peptide; 
 C ter  represents the C-terminal end of the peptide; 
 a, b, c and d independently represent 0 or 1; 
 e represents 0, 1, 2, 3 or 4; 
 f represents 0, 2 or 3; 
 Ac represents acetyl group; 
 E represents glutamic acid; 
 L represents leucine; 
 G represents glycine; 
 R represents arginine; 
 K represents lysine; 
 V represents valine; 
 X 18  represents an amino acid selected from the group consisting of alanine, 2-amino-isobutyric acid and leucine; 
 X 19  represents an amino acid selected from the group consisting of glutamine, Nε-acetyl-lysine and alanine; 
 I represents isoleucine; 
 Aib represents 2-amino-isobutyric acid; 
 X 25  represents an amino acid selected from the group consisting of methionine, norleucine, glutamine, Nε-acetyl-lysine and glutamic acid; 
 S represents serine; 
 T represents threonine; 
 X 28  represents an amino acid selected from the group consisting of tryptophan, 1-naphtylalanine, phenylalanine, tyrosine, α-methyl-tryptophane, α-methyl-phenylalanine and 5-hydroxy-tryptophane; 
 X 29  represents an amino acid selected from the group consisting of serine, threonine and α-methyl-serine; 
 X 30  represents an amino acid selected from the group consisting of lysine, 2-amino-isobutyric acid and α-methyl-lysine; 
 X 31  represents an amino acid selected from the group consisting of arginine, Nω-methyl-arginine, Nω,Nω′-dimethylmethyl-arginine, alanine and citruline; 
 X 32  represents an amino acid selected from the group consisting of lysine, alanine and Nε,Nε,Nε-tri-methyl-lysine; 
 X 33  represents an amino acid selected from the group consisting of leucine, lysine and Nε-acetyl-lysine; 
 (X 35 ) e  represents a polyethylene glycol derivative selected from the group consisting of PEG 2 , (PEG 2 ) 2 , (PEG 2 ) 3 , (PEG 2 ) 4 , PEG 2 DGA, (PEG 2 DGA) 2 , (PEG 2 DGA) 3 , (TTDS) 2 , (TTDS) 3 , PEG 4 , (PEG 4 ) 2 , PEG 8 , PEG 12 , PEG 24  and PEG 28 ; 
 gE represents gamma-glutamic acid; 
 X 37  represents the following structure: 
 
       
         
           
           
               
               
           
         
         in which: 
         -* is as defined in  claim 1 ; and 
         Z is selected from the group consisting of -gamma glutamic acid-palmitoyl (-gE-Palm), -(gamma glutamic acid) 2 -palmitoyl (-(gE) 2 -Palm), -(gamma glutamic acid) 3 -palmitoyl (-(gE) 3 -Palm), -(gamma glutamic acid) 3 -stearoyl (-(gE) 3 -Stea), -(gamma glutamic acid) 4 -stearoyl (-(gE) 4 -Stea), -(gamma glutamic acid) 4 -plamitoyl (-(gE) 4 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -gE-Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -Palmitoyl (-(PEG 2 ) 2 -(gE) 2 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 2 -(gE) 3 -Palm), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 3 -(gE) 3 -Palm), -(PEG 2 ) 4 -(gamma glutamic acid) 3 -Palmitoyl (-(PEG 2 ) 4 -(gE) 3 -Palm), -(PEG 2 ) 3 -(gamma glutamic acid) 4 -Palmitoyl (-(PEG 2 ) 3 -(gE) 4 -Palm), -PEG 12 -(gamma glutamic acid) 3 -Palmitoyl (-PEG 12 -(gE) 3 -Palm), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 2 -(gE) 3 -Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 3 -(gE) 3 -Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 4 -Stearoyl (-(PEG 2 ) 3 -(gE) 4 -Stea), -(PEG 2 ) 4 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 4 -(gE) 3 -Stea), -(PEG 2 ) 5 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 ) 5 -(gE) 3 -Stea), -(PEG 2 DGA)-(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA)-(gE) 3 -Stea), -(PEG 2 DGA) 2 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA) 2 -(gE) 3 -Stea), -(PEG 2 DGA) 3 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 2 DGA) 3 -(gE) 3 -Stea), -PEG 12 -(gamma glutamic acid) 3 -Stearoyl (-(PEG 12 )-(gE) 3 -Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -PEG 2 -Stearoyl (-(PEG 2 ) 2 -(gE) 3 -PEG 2 -Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -PEG 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -(gE) 2 -PEG 2 -(gE)-Stea), -(PEG 2 ) 2 -(gamma glutamic acid) 3 -PEG 2 -(gamma glutamic acid)-Stearoyl (-(PEG 2 ) 2 -(gE) 3 -PEG 2 -(gE)-Stea), -(gamma glutamic acid) 2 -(PEG 2 ) 2 -(gamma glutamic acid)-Stearoyl (-(gE) 2 -(PEG 2 ) 2 -(gE)-Stea), -(gamma glutamic acid) 2 -(PEG 2 ) 3 -(gamma glutamic acid)-Stearoyl (-(gE) 2 -(PEG 2 ) 3 -(gE)-Stea), -(PEG 2 ) 3 -(gamma glutamic acid) 5 -Stearoyl (-(PEG 2 ) 3 -(gE) 5 -Stea), -(gamma glutamic acid) 5 -Stearoyl (-(gE) 5 -Stea), -(PEG 2 ) 4 -(gamma glutamic acid) 4 -Palmitoyl (-(PEG 2 ) 4 -(gE) 4 -Palm); -(gamma glutamic acid) 4 -Lauroyl (-(gE) 4 -Lau), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Pentadecanoyl (-(PEG 2 ) 3 -(gE) 3 -Penta), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Heptadecanoyl (-(PEG 2 ) 3 -(gE) 3 -Hepta), -(PEG 2 ) 2 -(gamma glutamic acid) 2 -PEG 2 -(gamma glutamic acid)-Palmitoyl (-(PEG 2 ) 2 -(gE) 2 -PEG 2 -(gE)-Palm), -(TTDS) 2 -(gamma glutamic acid) 3 -Palmitoyl (-(TTDS) 2 -(gE) 3 -Palm), -(gamma glutamic acid) 4 -Pentadecanoyl (-(gE) 4 -Penta), -(gamma glutamic acid) 2 -Pentadecanoyl (-(gE) 2 -Penta), -(gamma glutamic acid) 4 -Myristoyl (-(gE) 4 -Myr), -(PEG 2 ) 4 -(gamma glutamic acid) 4 -Stearoyl (-(PEG 2 ) 4 -(gE) 4 -Stea), -(TTDS) 3 -(gamma glutamic acid) 3 -Palmitoyl (-(TTDS) 3 -(gE) 3 -Palm), -(gamma glutamic acid) 3 -Pentadecanoyl (-(gE) 3 -Penta), -(TTDS) 3 -(gamma glutamic acid) 3 -Pentadecanoyl (-(TTDS) 3 -(gE) 3 -Penta), -(PEG 2 ) 3 -(gamma glutamic acid) 3 -Eicosanoyl ((-PEG 2 ) 3 -(gE) 3 -Eico) and -(PEG 2 ) 3 -(gamma glutamic acid) 3 -docosanoyl ((-PEG 2 ) 3 -(gE) 3 -Doco); 
         or a salt or solvate thereof. 
       
     
     
       7. The peptide according to  claim 1 , having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, 11, 13-20, 23-43, 45-49, 56-58, 60-119, 121-177 and 180-193. 
     
     
       8. The peptide according to  claim 1 , having an amino acid sequence selected from the group consisting of SEQ ID NO: 14-20, 23-43, 45-49, 56, 57, 60-119, 121-125, 127-133, 135-160, 162, 164-177 and 180-193. 
     
     
       9. The peptide according to  claim 1 , having an amino acid sequence selected from the group consisting of SEQ ID NO: 14-20, 26, 27, 30, 31, 33, 36, 38-43, 45, 46, 48, 56, 60, 61, 63-76, 79-86, 88-93, 98-113, 115, 116, 121-125, 128-131, 133, 135-143, 145, 146, 148-154, 156-160, 162, 164-174, 177, 182-189 and 191-193. 
     
     
       10. The peptide according to  claim 1 , having an amino acid sequence selected from the group consisting of SEQ ID NO: 14-20, 27, 38-43, 48, 60, 61, 64, 65, 67, 70, 72-75, 79, 81, 82, 84, 88-93, 99-106, 108-112, 115, 122-125, 128, 130, 131, 133, 136-143, 145, 146, 148-154, 156-160, 162, 165-171, 173, 174, 182-187, 189, 191 and 193. 
     
     
       11. The peptide according to  claim 1 , having the amino acid sequence of reference SEQ ID NO: 81, 150 or 170. 
     
     
       12. The peptide according to  claim 1 , having an amino acid sequence selected from the group consisting of SEQ ID NO: 14, 16, 39-42, 74, 75, 82, 84, 89-91, 99, 102, 103, 105, 122, 125, 133, 136, 138, 142, 146, 150, 152, 156, 157, 159, 167-170, 183 and 185. 
     
     
       13. A pharmaceutical composition comprising at least one peptide according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable carrier. 
     
     
       14. A method for treating a disease or condition implicating the Relaxin family peptide receptor 1 (RXFP1) comprising administering to an individual in need of said treatment a peptide according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       15. The method according to  claim 14 , wherein the disease or condition is selected from the group consisting of fibrosis, fibrotic diseases, idiopathic pulmonary fibrosis, kidney diseases involving fibrosis, pulmonary hypertension, and preeclampsia. 
     
     
       16. The method according to  claim 14 , wherein the disease or condition is selected from the group consisting of heart disease and vascular disease. 
     
     
       17. The method according to  claim 16 , wherein the disease or condition is selected from the group consisting of acute or chronic heart failure, systolic or diastolic heart failure, coronary artery disease, atherosclerosis, microvascular angina, and cardiovascular complication of diabetes. 
     
     
       18. The method according to  claim 14 , wherein the disease or condition is a renal failure. 
     
     
       19. The method according to  claim 18 , wherein the disease or condition is selected from renal dysfunction in cirrhosis, chronic kidney disease, and acute kidney injury. 
     
     
       20. The method according to  claim 14 , wherein the disease or condition is fibrotic disease selected from the group consisting of systemic sclerosis, scleroderma, and fibromyalgia.